MS incidence and prevalence in Africa, Asia, Australia and New Zealand: A systematic review.

OBJECTIVES: Studies of multiple sclerosis (MS) incidence and prevalence from Africa, Asia, Australia and New Zealand are relatively scarce. We systematically reviewed MS incidence and prevalence in these regions including a standardized evaluation of study quality. METHODS: We searched MEDLINE and EMBASE databases for studies of MS prevalence or incidence in Africa, Asia, Australia and New Zealand published in English or French between January 1, 1985 and January 31, 2011. Study quality was assessed using a standardized tool. All steps of the review were performed in duplicate. RESULTS: Of 3925 citations identified, 28 studies met inclusion criteria and 21 of these were from Asia. Quality scores ranged from 1/8 to 8/8; the lowest scores were observed in studies from Asia (median 4/8, IQR 3,6). Prevalence was lowest in South African Blacks (0.22/100,000) and highest amongst Australian-born individuals in Australia (125/100,000). Prevalence increased over time in many countries. MS prevalence increased with increasing latitude only in some regions, and prevalence varied significantly with ethnicity. Eight studies reported incidence, which ranged from 0.67/100,000/year in Taiwan to 3.67/100,00/year in Australia. CONCLUSIONS: This comprehensive study provides an update of MS epidemiology in Africa, Asia, Australia, and New Zealand. Incidence and prevalence were lowest in Africa and Asia and highest in Australia, but many Asian studies were of poor quality. Use of consistent case ascertainment methods, standardized data collection tools, and similar outcomes would all improve study quality and comparability. The underlying basis of observed ethnic differences is an important area for future study.

Prescriptions filled during pregnancy for drugs with the potential of fetal harm.

OBJECTIVE: To assess the extent of prescriptions filled by pregnant women for drugs with recognised potential of fetal harm, and to document the outcomes of these pregnancies. DESIGN: Cross-sectional study. POPULATION: Quebec Pregnancy Registry. METHODS: We identified women who were pregnant during a five-year period and who were insured for prescription medications under the provincial drug plan. We obtained information on prescriptions filled during pregnancy for drugs with known potential of fetal harm. MAIN OUTCOME MEASURES: Prescriptions filled for study drugs during the first, second and third trimesters of pregnancy; termination of pregnancy (TOP) or delivery, and whether the baby was diagnosed with a major congenital malformation (MCM). RESULTS: Of 109 344 women, 56% filled at least one prescription for a medication during pregnancy; 6.3% filled at least one prescription for a drug known to pose a risk to the fetus. Overall, 47% (95% CI, 45.8-48.2) of pregnancies exposed to drugs under study ended in TOP versus 36.2% (95% CI, 35.9-36.5) of those not exposed; 8.2% (95% CI, 8.0-10.0) of live births were diagnosed with an MCM during the first year of life versus 7.1% (95% CI, 6.9-7.3) of those not exposed. CONCLUSIONS: This study documents an important level of prescriptions filled during pregnancy for drugs harmful to the developing fetus. The proportions of both TOPs and babies born with MCMs were elevated compared with the expected values. Clinicians caring for women during pregnancy should conduct a medication inventory prior to a planned pregnancy, or as soon as an unplanned pregnancy is recognised.

Persistent human papillomavirus infection as a predictor of cervical intraepithelial neoplasia.

CONTEXT: Human papillomavirus (HPV) infection is believed to be the central cause of cervical cancer, although most of the epidemiological evidence has come from retrospective, case-control studies, which do not provide information on the dynamics of cumulative or persistent exposure to HPV infection. OBJECTIVE: To assess the risks of cervical neoplasia related to prior persistent HPV infections. DESIGN AND SETTING: Longitudinal study of the natural history of HPV infection and cervical neoplasia in women residing in the city of São Paulo, Brazil, which was conducted between November 1993 and March 1997 and involved repeated measurements of HPV and lesions with follow-up until June 2000. PARTICIPANTS: A total of 1611 women with no cytological lesions at enrollment and HPV test results available from the first 2 visits. MAIN OUTCOME MEASURE: Cervical specimens taken for Papanicolaou cytology and HPV testing every 4 months in the first year and twice yearly thereafter. Incident cervical cancer precursor lesions ascertained by expert review of all cytology smears. RESULTS: The incidence rate of squamous intraepithelial lesions (SILs) was 0.73 per 1000 women-months (95% confidence interval [CI], 0.5-0.9) among women free of HPV at the 2 initial visits and 8.68 (95% CI, 2.3-15.1) among women with HPV type 16 or 18 infections persisting over both visits. Relative to those negative for HPV oncogenic types at both initial visits, the relative risk (RR) of incident SIL was 10.19 (95% CI, 5.9-17.6) for persistent infections with any known oncogenic HPV types. The equivalent RR of incident high-grade SIL was 11.67 (95% CI, 4.1-33.3). The RRs of lesions were considerably higher for persistent infections with HPV type 16 or 18. CONCLUSION: A strong relationship exists between persistent HPV infections and SIL incidence, particularly for HPV types 16 and 18.

The effect of timolol, betaxolol, and placebo on corneal sensitivity in healthy volunteers.

This study in sixty healthy volunteers investigated the effect of a single drop of either 0.5% timolol ophthalmic solution, 0.5% betaxolol ophthalmic solution, or placebo on corneal sensitivity as measured by the Cochet-Bonnet anesthesiometer. Corneal sensitivity was measured immediately prior to the drop and then 1, 3, 6, 10, 15 and 30 minutes after drop instillation. The timolol treated eyes showed a significant decrease at one minute after instillation. An increase in sensitivity occurred in the placebo group at 15 and 30 minutes. In the eyes treated with betaxolol, a significant reduction in corneal sensitivity was seen at every time point through the 10-minute measurement.

Changing therapy from timolol to betaxolol. Effect on intraocular pressure in selected patients with glaucoma. Timolol-Betaxolol Study Group.

Three hundred fifty-three patients whose intraocular pressure was controlled with a timolol maleate ophthalmic solution were studied. Following a baseline period, half were switched (masked and randomized) to treatment with a betaxolol hydrochloride ophthalmic solution and were followed up for 12 weeks. Intraocular pressure, signs, and symptoms were recorded at weeks 1, 4, 8, and 12. Those patients switched to the betaxolol ophthalmic solution had a significant increase in both ocular side effects (burning/stinging and tearing) and intraocular pressure at weeks 4, 8, and 12 when compared with those patients who continued to receive timolol.

The efficacy and safety of enalapril in moderate to severe essential hypertension.

When added to hydrochlorothiazide, enalapril is as effective as captopril in the treatment of moderate to severe hypertension. It is also effective when used as monotherapy, and may be incorporated into a regimen with diuretic and methyldopa or timolol for the treatment of more resistant patients. Enalapril has a good safety profile as measured by frequency of clinical and laboratory adverse experiences.

Overall tolerance and safety of enalapril.

To date, more than 5000 patients have had experience with enalapril. Over 1000 subjects have been exposed to the drug for more than one year and approximately 600 for over two years. In controlled trials, 2249 subjects, who included normal volunteers and patients with hypertension and congestive heart failure, have received enalapril alone or concomitantly with hydrochlorothiazide or other antihypertensive agents. There have been no deaths attributed to enalapril. The incidence of serious adverse experiences in controlled trials was similar to placebo, and was not higher in the elderly. The incidence of adverse experiences was not dose-related. Drug discontinuation due to adverse experiences was 3.5%, similar to placebo, and approximately half that of control drugs. Serious laboratory adverse experiences were rare. Enalapril attenuated the adverse metabolic effects of hydrochlorothiazide, particularly hypokalaemia. Skin rash occurred in approximately 1.0% of patients. One case of transient taste loss occurred on enalapril, and one on enalapril in combination with hydrochlorothiazide. Neutropenia and agranulocytosis were not encountered. Mean white blood cell counts did not change overall. Most patients (approximately equal to 80%) show no change or an improvement in renal function on enalapril. Discontinuation of concomitant hydrochlorothiazide usually normalized renal function. Enalapril is well tolerated in renal insufficiency. Azotaemia may occur in bilateral renovascular hypertension. Proteinuria was rarely seen and often improved on enalapril. Compassionate use protocols have been available to patients either resistant or intolerant to captopril. Of 68 patients admitted for captopril-related skin rashes, only five recurred on enalapril.(ABSTRACT TRUNCATED AT 250 WORDS)

Changes in serum thyrotropin (TSH) in man during halofenate administration.

Halofenate, a serum lipid-lowering agent which inhibits binding of thyroid hormone to thyroxine-binding globulin (TBG), was administered daily for 14 days to 8 hypothyroid subjects with elevated TSH concentrations as a result of incomplete thyroxine (T4) therapy. Drug administration resulted in mean increases in serum dialyzable fraction T4 (DFT4) of 52% over pretreatment levels (P less than 0.01) and in dialyzable fraction triiodothyronine (DFT3) of 26% in 7 subjects, (P less than 0.01). During halofenate treatment in these 7 subjects, serum TSH concentrations decreased significantly (mean = 39%, P less than 0.01) when DFT4 and DFT3 were increased by halofenate. In only two subjects was there a convincing temporal relationship between increased serum absolute free T4 (AFT4) and decreased serum TSH concentrations. Contrary to what would be predicted from the "free hormone hypothesis", changes in serum TSH concentration in these hypothyroid patients appeared to relate primarily to changes in the free fraction of circulating T4 and T3 (DFT4, DFT3), rather than to alterations in AFT4 or AFT3. Halofenate did not alter serum TBG binding capacity. An eighth subject did not show increased DFT4 and DFT3 during halofenate treatment despite achievement of therapeutic serum levels of the agent; in this patient, serum TSH levels rose progressively throughout the period of inadequate T4 replacement and halofenate administration. In hypothyroid patients, short-term halofenate use suggests that the pituitary-thyroid hormone feedback circuit can respond to increases in serum DFT4 and DFT3 in the absence of detactable increases in absolute free hormone concentrations.